the many faces of chondrosarcoma of bone - achot.cz · the many faces of chondrosarcoma of bone ......

501/ ACTA CHIRURGIAE ORTHOPAEDICAEET TRAUMATOLOGIAE ČECHOSL., 78, 2011, p. 501–509 CURRENT CONCEPTS REVIEW

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The Many Faces of Chondrosarcoma of BoneOwn Cases and Review of the Literature with an Emphasis on Radiology, Pathologyand Treatment

Mnoho podob chondrosarkomu. Vlastní případy a přehled literatury s důrazem na radiologii, patologii a léčbu

G. W. HERGET1, 3, M. UHL2, O. G. OPITZ3, C. P. ADLER4, N. P. SÜDKAMP1, S. KNÖLLER1

1 Department of Orthopaedics and Traumatology, University Medical Center, Freiburg i. Br., Germany2 Department of Rdiology, St. Josefskrankenhaus, Freiburg i. Br., Germany3 Tumozentrum Ludwig Heilmeyer – Comprehensive Cancer Center Freiburg, University Medical Center, Freiburg i. Br., Germany4 Institute of Pathology, Reference Center of Bone diseases, University Medical Center, Freiburg i. Br., Germany

SUMMARY

Chondrosarcoma is the third most frequent primary malignant tumor of bone, constituting up to 16% of the malignantosseous neoplasms. Up to date several genetic alterations and markers were described concerning the pathogenesis andthe progression of the chondrosarcoma, which represents actually a heterogeneous group of different types including con-ventional intramedullary, clear cell, myxoid, mesenchymal, and dedifferentiated chondrosarcoma.

The pathologic appearance varies, however, in general they grow with a lobulated pattern. Histologically the hyaline car-tilage demonstrates high water content and typically enchondral ossification is apparent. Imaging reflect this while radio-graphic findings suggest the diagnosis when the typical “ring-and-arc” chondroid matrix mineralization, endosteal scallo-ping and soft-tissue extension were apparent.

The CT is used for detecting the mineralization of the matrix, especially when it is subtle or when the lesion is locatedin complex areas. MRT is the method of choice to detect the high water content of these lesions with a high signal inten-sity with T2-weighting and its bone marrow extend.

Surgical resection is the primary and preferred treatment modality for most individuals with localized disease. In selec-ted cases of the Grad I conventional chondrosarcoma curettage should be discussed. Systemic chemotherapy may be con-sidered in variant forms such as mesenchymal or dedifferentiated chondrosarcomas.

In knowledge of the “many faces” of the primary chondrosarcoma individualized patient assessment and optimal clini-cal management is possible.

Key words: chondrosarcoma, CT, MRT, PET, treatment.

INTRODUCTION

Chondrosarcoma is, after multiple myeloma andosteogenic sarcoma, the third most common primarymalignant tumor of bone (1). Tumors that arise de novoare called primary chondrosarcomas, secondary chond-rosarcomas arise from a preexisting benign cartilaginouslesion such as enchondroma or osteochondroma (16,19).

Up to date several genetic alterations and markerswere described regarding the pathogenesis and progres-sion of the chondrosarcoma, including the PTHR1 muta-tion, the hedgehog signaling pathway, p53, insulin-likegrowth factor, cyclin-dependent kinase 4 and others (4,18)

Chondrosarcomas are a heterogeneous group oftumors. More than 90% are designated conventionalchondrosarcomas. Approximately 90% of these are low-grade to intermediate-grade tumors (grade 1 or 2), whichhabour an indolent clinical behaviour and low metasta-tic potential; only 5–10% are grade 3 lesions, which havehigh metastatic potential (8, 11). Its variants are rare and

several types are described, including conventionalintramedullary, clear cell, juxtacortical, myxoid, mesen-chymal, extraskeletal, and dedifferentiated chondrosar-coma (16, 29). Depending on their location, they arecategorized as central, peripheral, or juxtacortical (peri-osteal) tumors.

Radiographic findings strongly suggest the diagnosisof chondrosarcoma by demonstrating a lesion with typi-cal chondroid matrix mineralization (ring-and-arc pat-tern) and aggressive growth features (21). In addition tothe conventional radiography, bone scintigraphy, com-puted tomography (CT), and magnetic resonance tomo-graphy (MR) are employed for the diagnosis and stagingof the tumor (21, 29).

Surgical resection is the preferred treatment modali-ty for most individuals with localized disease. In selec-ted cases of the Grad I conventional chondrosarcomacurettage is discussed. And, systemic chemotherapy maybe considered in some forms such as mesenchymal ordedifferentiated chondrosarcomas

In this article the various types of the chondrosarco-ma are discussed and illustrated.

s_501_509_herget_test_acta_sloupce 12/6/11 6:27 AM Stránka 501

lear pleomorphism than grade 2 tumors. The nuclei varyin size, and often include giant nuclei with a very den-se chromatin content. Chondroid matrix is sparse orabsent, and the small amount of intercellular materialpresent is often myxoid. Foci of necrosis are almost inva-riably seen and are more frequently extensive (1, 9, 14).

Radiographs typically reveal a mixed lytic and scle-rotic appearance. The lesions are mostly greater than4 cm in size, many of them are greater than 10 cm (23).The tumor, typically growing with a lobular architec -ture, frequently causes endosteal scalloping with or without cortical penetration. Areas with mineralizationof the matrix (calcification) appear granular and havea “ring-and-arc” pattern. This characteristic usuallyallows confident radiologic diagnosis of a cartilaginouslesion. Nonmineralized regions (higher-grade chondro-

Conventional intramedullary chondrosarcoma is themost common type of primary chondrosarcoma. Theyappear at any age, the average being 46 years (1). Cli-nical symptoms are nonspecific: pain, a palpable soft-tissue mass and pathologic fractures are common (23,25).

The tumor can involve any bone. In the axial skele-ton it mostly could be found in order to appearance inthe ribs, spine, scapula and sternum. It rarely affectslocations like the craniofacial region, neck (arising fromthe hyoid as well as laryngeal and tracheal cartilage),forearm, clavicle, sesamoids, and the short tubular bonesof the hands and feet. However, the most common ske-letal locations are the long bones, especially the femurand the proximal humerus, involving the metaphysic in50% of cases, followed by the diaphysis in 36%).Tumors in the epiphysis are again unusual (14, 23, 25).

A three-grade system is commonly used: Grade 1 le -sions (low grade) have chondrocytes with small densenuclei, that vara somewhat in size and and show a mode-rate degree of polymorphy. The stroma is predominant-ly chondroid. Myxoid areas are usually sparse or absent.Grade 2 chondrosarcomas (intermediate grade) have lesschondroid matrix and greater irregularity in the distri-bution of the tumorous chondrocytes, which may oftenbe found packed closely together in groups. The chond-rocyte nuclei are enlarged, bi- and multinucleatedchondrocytes occur. Necrotic areas may be present, thestroma is frequently myxoid. Grade 3 chondrosarcomas(high grade, Fig. 1a) exhibit greater cellularity and nuc-

502/ ACTA CHIRURGIAE ORTHOPAEDICAEET TRAUMATOLOGIAE ČECHOSL., 78, 2011 CURRENT CONCEPTS REVIEW

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Fig. 1a. Conventional intramedullary chondrosarcoma of thescapula in a 65-y-old man. The typical popcorn-like calcifi-cations within the large tumor-mass are best seen in the CT-scan.

Fig. 1b-c. The most strikingfeature of the chondrosarco-ma grade 3 is the polymorp-hy of the tumor cells. Notethe nodule, which is fairlysharply delineated by a nar-row connective tissue sep-tum (HE, 40x).

sarcomas have larger areas that are not calcified) appe-ar translucent, reflecting the high water content of hyaline cartilage. Aggressive “moth-eaten” and/or per-meative bone lysis may be seen with higher-gradechondrosarcomas; more frequently they are associatedwith mesenchymal, myxoid, and dedifferentiated celltypes (21, 28). Because of the relatively slow growth ofthe chondrosarcoma, the cortex responds by remode-ling, thickening, and periosteal reaction (reaction isuncommonly associated with enchondroma).

The CT allows detection and characterization of mat-rix mineralization (Fig. 1b-c), however, neither theextent nor the presence can help to differentiate longbone enchondroma from chondrosarcoma. To distingu-ish conventional chondrosarcoma from enchondroma,following criteria are helpful: entrapment/destruction ofthe trabecular bone is the hallmark of a chondrosarco-ma. And, scalloping greater than two-thirds the normalthickness of the long bone cortex is strong evidence ofchondrosarcoma. Cortical response, including corticalthickening and periosteal reaction, is equally welldemonstrated with CT and radiography (21, 23); iden-tification of soft-tissue extension on CT scans is morefrequent than on radiographs and it occurs in about 60%of long bone chondrosarcomas.

MR imaging provides the best method for detectingthe extent of marrow involvement (26). On T1-weigh-ted MR images, marrow replacement appears as low tointermediate signal intensity. The typical lobulatedarchitecture is seen best at the lesion margin. The non-mineralized components have high signal intensity onT2-weighted images, reflecting the high water contentof the tumor-cartilage. Areas of matrix mineralizationhave low signal intensity with all MR sequences. This

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of cases (17, 21). A peripheral sclerosis, simulatinga benign lesion, is detected in 20% of the cases, and in30% of cases mild expansile remodeling of bone is seen.

CT demonstrates matrix mineralization, corticaldestruction, and/or soft-tissue extension. MR imagingtypically shows homogeneous intermediate signal inten-sity with T1-weighted sequences and heterogeneoushigh signal intensity with T2-weighted sequences (17,24). Because of the epiphyseal location, clear cellchondrosarcoma can be difficult to distinguish fromchondroblastoma, however, patients with clear cellchondrosarcoma are usually older than those withchondroblastoma, and imaging features that suggestclear cell chondrosarcoma include a large lesion, lack ofsurrounding edema, high signal intensity on T2-weigh-ted MR images and more calcifications (chondroblasto-mas: extensive surrounding bone marrow edema andsoft-tissue edema, areas of low signal intensities in T2-weighted images (17).

Although it is a low-grade tumor, lesions are ofteninadequately treated with curettage, which leads torecurrence, whereas adequate aggressive initial surgicalresection with joint arthroplasty is usually curative (18).Overall recurrence rate is 16%, and approximately 15%of patients die of the disease. Metastases to the lung,brain, and bones have been reported (26, 29).

Juxtacortical chondrosarcomaare also rare lesions,accounting for 2% of all chondrosarcomas (4, 14). The-se tumors, which arises on the surface of the bone, havealso been referred as periosteal and parosteal chondro-sarcoma. They most frequently affect adults in the 3rd

Fig. 2b. Clear-cell chondrosarcoma in a 47-y-old women withhip pain. The osteolytic lesion in head of the proximal femurwith its typical origin in the epiphysis.

feature often creates marked heterogeneity on T2-weighted MR images. However, areas of low signalintensity on T2-weighted MR images are nonspecificand have numerous other potential causes, e.g. fibroustissue with high collagen content. Peritumoral edema,which is best seen in the T2-weighted images, also sug-gest chondrosarcoma over enchondroma. And soft-tis-sue extension with mass formation essentially excludesthe diagnosis of enchondroma (15).

In bone scintigraphy the majority of long bone chond-rosarcomas reveal marked increased radionuclide upta-ke compared with that in the anterior iliac crest. This isin contrast to long bone enchondromas (increased acti-vity up to 20% of cases).

Basically, there are two categories for surgical treat-ment: (Intralesional) Curettage, adjunct chemical orthermal ablation, and cementation or bone grafting ofthe defect versus wide excision with structural graft orreconstruction (10).

Acceptable oncologic and functional results havebeen observed in patients with grade 1 chondrosarcomatreated with curettage and cryosurgery alone (14).However, local recurrence is not unusual if there is ina-dequate resection (9, 26). Wide excision is performendin higher grade chondrosarcomas, in some cases also inthe grade 1 chondrosarcoma. Large lesions and chond-rosarcomas in anatomic locations that do not allow ade-quate margins or complete excision (such as the spine,craniofacial region, ribs, pelvis) have an obvious incre-ased risk of local recurrence and metastatic disease (24,26). The overall 5-year survival rates for chondrosarco-ma are 90% in grade 1, up to 80% in grade 2, and 40%in grade 3 tumors, whereas the 10-year survival rates are85% (grade 1), up to 60% (grade 2), and up to 30% (gra-de 3) (24, 26).

Clear cell chondrosarcomais a rare bone neoplasmthat constitutes approximately 1%–2% of all chondro-sarcomas and 0.2% of all primary bone tumors (9, 11,26). Patients are most commonly affected between the3rd and 5th decade, with men being affected twice asoften as women (28). Symptoms include localized pain,decreased range of motion of the adjacent joint and pat-hologic fractures.

It affects the long tubular bones in 90% of cases, witha particular predilection for the proximal femur (60%)and proximal humerus (20%). There is also a markedpredilection for epiphyseal involvement, althoughmetaphyseal extension is common (Fig. 2a). Flat bonesare affected in up to 10% of cases (1, 11, 28)

Histologically, lesions show unambiguous cartilagestructures that make one think of a benign chondrobla-stoma. The most striking feature is, that tumor revealnumerous cells with vacuolated cytoplasm containinglarge amounts of glycogen (clear cell chondrocytes) thatoften lie between heavily calcified trabeculae (Fig. 2b).In contrast to conventional chondrosarcoma, they fre-quently contain large areas of hemorrhage and cyst for-mation (1).

Radiographs reveal a predominantly lytic lesion andmatrix mineralization is apparent in about 25% – 30%

Fig. 2a. The tumor cells of theclear-cell chondrosarcomaare large and have a volumi-nous, very pale cytoplasma.They are sharply delineatedby a prominent cell border.Nuclei are roundish or ovaland hyperchromatic, but fair-ly isomorphic. Multinuclea-ted chondroblasts are rareand there a are no mitosis(HE, 40x).


Radiographs demonstrate a lobulated mass on the sur-face of bone. Typical chondroid matrix mineralizationis usually present. The underlying cortex is frequentlythickened with associated saucerization and Codman tri-angles (7). Matrix mineralization is better seen on CTscans (Fig. 3 c/d). In the MR the lesion shows a low hete-rogeneous signal intensity with T1-weighted sequencesand heterogeneous high signal intensity with T2-weigh-ted sequences. Use of contrast material with CT or MRimaging often reveals peripheral and septal enhance-ment. The medullary canal is typically not involved. Dif-

ferential diagnosis include juxtacortical chondroma,parosteal osteosarcoma, and periosteal osteosarcoma(7). Lesion size is often the best differentiating feature,with juxtacortical chondromas being invariably smaller(2–3 cm in size) than juxtacortical chondrosarcoma(3–14 cm, 5 cm average). Differentiating between jux-tacortical chondrosarcoma and periosteal osteosarcoma:the latter is characterized by the presence of periostealreaction perpendicular to the cortex on radiographs,young patient age (10–25 years), diaphyseal location,and a osteoblastic component (1, 11). Parosteal osteo-sarcoma may be radiologically similar to juxtacorticalchondrosarcoma but it usually has a stalk of attachmentto the cortex and extensive osteoid.

Treatment of juxtacortical chondrosarcoma is widesurgical resection. Local recurrence and metastatic dise-ase have been reported, but the prevalence is low, evenwith higher-grade lesions (24, 26).

Myxoid chondrosarcomarepresents about 2% of allchondrosarcomas of bone. Affected individuals are typi-cally male adults with a mean age 50 years, and half ofthe reported cases have occurred in the femur (1, 9).

Histologically, the tumor was revealed to have a nodu-lar arrangement with rather well-defined tumor lobules.Individual tumor cells varied slightly in size and shape(usually round to oval) and were separated by abundantmyxoid stroma (Fig. 4a) (1).

covered by a fibrous pseudocapsule that is continuouswith the underlying periosteum. Histologically, the car-tilaginous part of the tumor shows the characteristic pic-ture of a moderately highly differentiated chondrosar-coma and shows a similar appearance as intraosseouschondrosarcomas (Fig. 3b).


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to 4th decade of life. Clinical signs are a palpable andpainless, slowly growing tumor. Lesions are most fre-quently seen on the surface of long bones, particularlythe posterior distal femoral metaphysis or diaphysis.

At gross pathologic examination, juxtacortical chond-rosarcoma arises on the surface of bone (Fig. 3a) and is

Fig. 3a. Juxtacortical chond-rosarcoma of the proximalfemur arises on the surface ofbone (masceration speci-men). From: Adler C.P. Kno-chenkrankheiten, Springer2005

Fig. 3b. The typical histological appearance of the juxtacorti-cal chondrosarcoma shows lobulated cartilaginous tissue inwhich chondrocytes are irregularly distributed. Most of themhave a single nucleus an lie within large cell nests. The nuc-lei are often only sketchily polymorphic, sometimes roundish(HE, 40x).

Fig. 3c-d. Juxtacortical chondrosarcoma: Anteroposteriorshoulder radiographs show tumor mass on the surface of bone(a). Typical calcifications in the juxtacortical lesion are visib-le in the CT-scan of the proximal humerus (b)

Fig. 4a. The microscopic appearance of the myxoid chondro-sarcoma shows individual tumor cells, focally binucleated,that resemble chondroblasts within abundant myxoid stroma.No hyaline cartilage formation is seen. Areas of increased cel-lularity, marked nuclear pleomorphism, and mitotic activitywere apparent (HE, 40x).

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Radiographics shows a permeative pattern of osseousdestruction and an associated soft-tissue mass. Matrixmineralization is frequently apparent on CT scans butnot extensive. Both CT and MR imaging demonstratethe markedly high water content with very high signalintensity in fat-suppressed T2-weighted sequences(Fig. 4b–d). They frequently contains hemorrhage,which appears as areas of high signal intensity in all MRsequences, particularly in the large associated soft-tis-sue components. Enhancement after intravenous admi-nistration of contrast material is often only mild and sep-tal to peripheral in pattern (21, 28).

The lesion has a more aggressive clinical course thanconventional intramedullary chondrosarcoma. Initialwide local resection is considered the treatment of cho-ice. Patients commonly developing distant metastasesand local recurrence (26).

The most frequent metastatic sites are the lungs andregional lymph nodes. Metastases may even occur aftera long delay. Patients with intraosseous lesions have a 5-year survival rate of 60%.

Mesenchymal chondrosarcoma accounts for up to12% of all chondrosarcomas of bone (9, 22). It is anaggressive high-grade tumor with a strong tendency tometastasize. Clinical symptoms are nonspecific: pain,swelling, and a palpable soft-tissue mass. Men andwomen are equally affected, most frequently in the 2ndto 4th decade of life. Commonly lesions affects the axi-al skeleton, the ribs, jaws and long bones, mostly in a dia-physis. Although most cases arise in previously normalbone, it may occur as a secondary lesion associated withpre-existing fibrous dysplasia (23).

Histologically, one can recognize the very clear lobu-lar and nodular formation. The nodules of varying sizeare fairly sharply separated by narrow connective tissuesepta which contain blood vessels. The characteristichistologic feature are large components composed ofsmall, uniform, round to spindle-shaped cells, resemblethose of Ewing sarcoma, and focal admixed areas ofmalignant cartilaginous tissue (Fig. 5a) (1).

Radiographs show aggressive bone destruction witha moth-eaten to permeative pattern and ill-defined mul-tilayer periosteal reaction. The tumor is often very lar-ge, with extensive extraosseous components. Areas ofcharacteristic “ring-and-arc” chondroid calcificationsare seen in up to 70% of cases, although they are oftennot extensive (3, 22).

CT shows aggressive bone destruction with a largeassociated soft-tissue mass and chondroid minerali -zation. MR images show low to intermediate signalintensity with T1-weighted sequences and intermedi-ate signal intensity with T2-weighted sequences(Fig. 5 b–c). The pattern of enhancement varies fromhomogeneous to heterogeneous but is often diffuse andlacks the typical cartilaginous septal and peripheralenhancement.

Tumor require a wide local excision when possible.Local recurrence is common, as are metastases (lung,regional lymph nodes, and bone). Patients with intraos-seous lesions have a 5-year survival rate of 42% anda 10-year survival rate of 28% (22).

Dedifferentiated chondrosarcoma represents approxi-mately 10% of all chondrosarcomas and about 1%–2%of all primary bone tumors. Patients are usually betwe-en 50 and 70 years old, men and women are affectedequally. Clinical presentation is pain in the most cases,

Fig. 4b–d. Myxoid chondrosarcoma: the outer border of the lesion is well demonstrated in T1 weighted image (b). The veryhigh-signal in the T2 weighted image (c) correlates to the typically high water content of this lesion (d).

Fig. 5a. The characteristic histologic feature of the mesen-chymal chondrosarcoma are large components composed ofsmall, uniform, round to spindle-shaped cells, resemble thoseof Ewing sarcoma, and focal admixed areas of malignant car-tilaginous tissue (HE, 40x).

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Fig. 5b–c. Mesenchymal Chondrosarcoma show aggressivebone destruction, with a moth-eaten to permeative pattern andill-defined multilayer periosteal reaction. The tumor is largewith extensive extraosseous components (b): T1 weightedtransversal MRI; (c): T2 weighted coronal MRI-scan).

followed by pathologic fracture (31%) and soft-tissuemass (29%) (14, 26). The majority of lesions occur cent-rally in the medullary bone. Locations mostly includingthe femur, pelvis and the humerus.

Histologically the tumor shows distinct foci that havededifferentiated into a more aggressive noncartilaginous

component, which is most frequently malignant fibroushistiocytoma, osteosarcoma, or fibrosarcoma (Fig. 6a)(1). The most striking feature is the large number of cells:on the one hand distended chondrocytes of various size,which posseses polymorphic nuclei; on the other handthe highly sarcomatous connective tissue with small den-sely loaded hyperchromatic nuclei which are markedlypolymorphic. The abrupt transition from neoplastic car-tilage to spindle-cell sarcomatous tissue is very charac-teristic (1).

Imaging findings vary, depending on the proportionof conventional chondrosarcoma that has transformed toa noncartilaginous high-grade malignancy (21). As thehigh-grade noncartilaginous focus increases in size,there is a progression of aggressive bone lysis, a dec -rease in matrix mineralization, and soft-tissue expansi-on is invariably seen (Fig. 6b–d). CT and MR may the-refore demonstrate two distinct areas: the low-gradeconventional chondrosarcomatous elements with previ-ously described pattern on imaging, and the noncartila-ginous component with variable signal intensity on T2-weighted MR images, lower in signal intensity thanthe conventional chondrosarcomatous component). Ima-ges obtained with i.v. contrast material demonstrate mildseptal and peripheral enhancement in the lower-grade(chondrosarcomatous) component as opposed to promi-nent diffuse enhancement in the high-grade noncartila-ginous areas (21, 28).

The tumor is a highly lethal malignancy, despite ade-quate aggressive initial wide surgical resection or evenamputation. Metastases occur early, are frequent, andcommonly involve the lungs, lymph nodes, and viscera(14). Most patients die within 2 years.

Further imaging modalitiesBone scintigraphy displays the activity of bone meta-

bolism and has a well established place in the diagnosisof bone malignancies. Radiotracer uptake in chondro-sarcoma was described to be variable, but often intenseuptake was found (20). Tracer distribution can rangefrom homogeneous to inhomogeneous and irregularuptake, sometimes with less uptake in the center of thelesion than around its periphery (“doughnut” sign).However, a typical pattern of distribution demonstratesareas of focal increased uptake throughout the tumour

Fig. 6a. The most striking feature in the dedifferentiated chond-rosarcoma is the large number of cells. One can seen on theone hand tumorous cartilaginous tissue with distended chond-rocytes of various sizes, which posses polymorphic nuclei. Onthe other hand, there is highly cellular sarcomatous connecti-ve tissue (HE, 40x).

Fig. 6b-d. Dedifferentiated chondro-sarcoma: Anteroposterior knee radio-graphs demonstrates a lytic lesionwith a permeative pattern and extra-osseous tumor mass (b). The T2 weigh-ted fat-suppressed MRI reveals not thehigh-water content of other cartilagetumors (c). The T1 weighted MRI afteri.v.-contrast-medium shows a remar-kable enhancement of gadolinium wit-hin the viable tumor (d).

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(20). Nevertheless, a strong correlation between inten-sity or pattern of uptake and histological grades was notfound (28). Bone scintigraphy can be used to excludefurther skeletal lesions (Fig. 7a–b).

Positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) is able to detect FDGuptake in cells with high metabolic activity and can beused for the detection and characterisation of malignantlesions (Fig. 8). The uptake intensity of PET tracers canbe determined reliably by the use of standardised upta-ke values (SUV).

Several publications reported increased uptake of thisradiotracer in chondrosarcomas, showing a good corre-lation of SUV and tumour grade (5, 12). Significant dif-ferences in the uptake levels between low- (grade I) andhigh grade (grade II und III) chondrosarcomas werereported. Furthermore, pretherapeutic tumour SUV isa useful parameter for predicting patient outcome interms of local relapse or metastatic disease (5).

Although available studies do not distinguish betwe-en the different subtypes of chondrosarcoma, neverthe-less generally higher SUV than in other subtypes wasreported in the extraosseous myxoid subtype (5).

Beside the application of FDG PET in the primarydiagnosis of chondrosarcoma, it can be a useful tool for

the diagnosis of metastatic disease and tumor recurren-ce in follow-up (12), especially in cases of limitationsof CT and MRI due to metallic prosthesis after tumouroperation. For biopsy planning, FDG PET can be usedto localize the tumor site within the highest metabolicactivity for selective sampling in cases of heteroge neouscartilage lesions (12).

In general, surgical resection is the primary and pre-ferred treatment modality for individuals with localizeddisease. Radiation therapy is only appropriate for pal -liation of disease-related symptoms. The treatment ofadvanced, metastatic disease is particularly challenginggiven the recognition that conventional chemotherapyhas proven to be largely ineffective. Systemic chemo -therapy may be considered in different forms such asmesenchymal or dedifferentiated chondrosarcomas(24).

CONCLUSIONS

Chondrosarcoma is the third most common primarymalignant tumor of the bone, representing up to 16%.Although the pathologic appearance varies within thedifferent types, they grow with lobular type architectu-re and demonstrate enchondral ossification.

The radiographic appearances reflect the pathologicfeatures: typically a ring-and-arc matrix mineralization,endosteal scalloping and soft-tissue extension could bedetected (tab. 1). CT detects the matrix mineralizationand depth of endostal scalloping. MR imaging shows thehigh water content seen in conventional, juxtacortical,and myxoid chondrosarcomas as high signal intensitywith T2-weighted sequences. High-grade chondrosar-comas (mesenchymal and dedifferentiated lesions) fur -thermore contain areas of matrix mineralization thatsuggest a chondroid neoplasm but also show aggressivepatterns of bone destruction and large associated soft-tissue masses.

Radiotracer uptake in chondrosarcoma is variable.A typical pattern of distribution demonstrates areas offocal increased uptake throughout the tumour. Beside inthe primary diagnosis of chondrosarcoma, PET can bea useful tool for the diagnosis of metastatic disease andtumor recurrence, especially in cases of limitations ofthe use of CT and MRI due to metallic prosthesis aftertumor operation.

Surgical resection is the primary and preferred treat-ment modality for the most individuals with localizeddisease. In selected cases (grade I tumors) the intralesio -nal curettage should be considered.

On a molecular level, several oncogenic pathwayshave been associated with tumor initiation and/or pro-gression, but not all pathways identified in such studiesare likely to lead to effective targeted therapies (4).However, systemic chemotherapy may still be an op tionin the mesenchymal or dedifferentiated chondrosarco-ma (4, 18)

Acknowledgement. We thank Christoph Rottenbur-ger, M.D. (Nuclear Medicine Physician, Freiburg, forhis comments of the use of the PET in chondrosarcoma.

Fig. 7a-b. Bone scintigraphy of a patient with grade I chond-rosarcoma of the left elbow. a. Early (blood pool) scan, sho-wing just slightly enhanced extravasal tracer accumulation inthe area of the left elbow (arrow). b. In the late (mineralizati-on) scan, intense, predominantly homogeneous tracer uptakecan be seen at the tumour site.

Fig. 8. FDG PET scan of a patient with metastasic high gra-de chondrosarcoma in coronar slices. Multiple bones meta-stases with intense tracer uptake (arrows). Physiologic traceruptake can be seen in brain, heart muscle, kidneys and urinebladder.



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Table 2. Typical radiological criteria of chondrosarcoma (1, 21, 28)

Conventional Chondrosarcoma – mixed lytic and sclerotic appearance– geographic and multilobulated bone lysis– endosteal scalloping (> 2/3 of the cortex)– cortical remodeling, cortical thickening, and periosteal reaction

Juxtacortical Chondrosarcoma – lytic lesion, matrix mineralization (30% of the cases)– 95% epiphyseal location– peripheral sclerosis (20% of the cases)– mild expansile bone-remodeling (30% of cases)– T1: intermediate signal intensity– T2: heterogeneous high signal intensity

Clear Cell Chondrosarcoma – lobulated mass on the surface of bone– chondroid matrix mineralization– T1: heterogeneous signal intensity– T2: heterogeneous high signal intensity

Myxoid Chondrosarcoma – permeative pattern of osseous destruction– associated soft-tissue mass– matrix mineralization (not extensive)– T2: high signal intensity– hemorrhage: areas of high signal intensity with all MR sequences

Mesenchymal Chondrosarcoma – aggressive bone destruction: moth-eaten to permeative pattern– ill-defined periosteal reaction, often extraosseous components– areas of ring-and-arc chondroid calcifications (70% of case)– T1: intermediate signal intensity– T2: intermediate signal intensity

Dedifferentiated Chondrosarcoma – aggressive bone lysis– invariable matrix mineralization and soft-tissue expansion– noncartilaginous component with variable signal intensity on T2

weighted MR – mild septal and peripheral enhancement in the lower-grade

chondrosarcomatous component; prominent diffuse enhancementin the high-grade noncartilaginous areas

Conventional CS Clear Cell CS Juxtacortical CS Skelettal Myxoid CS Mesenchymal CS Dedifferentiated CS% of all CS 75 2 < 2% 10 2 10Precursor lesion Enchondroma None Osteochondroma? None Fibrous Dysplasia? Conventional CSOccurrence Enchondromatosis none Osteochondromatosis? none none rarely in En-with syndrome /Osteochondro-

matosisAge any age, any age, mostly peak incidence mean age 50 years any age, mostly peak incidence

average 46 years between 3rd in the third in the 2nd to 4th between 5th and 7th and 5th decade to fourth decade decade of life decade

Main location pelvis, prox. long tubular bones short tubular bones long bones, especially axial skeleton, femur, pelvis Humerus and femur, with predilection for and proximal the femur the ribs, and humerusribs the proximal femur Humerus jaws and long

and humerus bones, mostlyin a diaphysis

Histological grading Grad I-III low-grade Grade I-III low-grade high-grade high-gradeSensitivity none low none low possible role possible role to chemotherapie of Chemotherapy of ChemotherapySensitivity low low low lowto radiotherapieSurgery High-grade: Wide resection, if necessary followed by a site-appropriate reconstruction (custom or modular endoprosthetics, allograft bone,

or autologous bone e.g.)Low-grade: There is a trend away from wide resection in selected Grade 1 tumors: surgery is an intralesional procedure (curettage with a high-speed burr to the surrounding bone) with or without treatment of the defect cavity with a local adjuvant therapy (phenol, freezing the bone). The defect can be reconstructed with allograft or autologous bone grafting or polymethylmethacrylate (bone cement) with or without internal fixation of the bone.

Survival Grade I: 83% roughly 25% of Overall 5-year 5-year survival rate: 90% 5-year survival rate: 5-year-survival Grade II: 64% patients experience metastasis-free 54.6% rate: 10.5%Grade III: 29% local recurrences of survival: 83%. 10-year survival

their tumors or suffer 5-year metastasis-free rate: 27.3%metastasis, but survival for grade tumor-related death 2 tumors: 50%,is uncommon, grade 1 tumors particularly when 94%the lesion has been completelyresected en bloc

Table 1. Clinical characteristics of the subtypes of chondrosarcoma (CS) of bone (2, 4, 13, 18, 22, 27)



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Corresponding author:Georg W. Herget, M.D., Ph.D.Department of Orthopedics and Traumatology /Comprehen-sive Cancer Center Freiburg (CCCF)University Hospital FreiburgHugstetterstr. 55, 79106 Freiburg i. Breisgau, GermanyE-mail: [email protected]

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